Technical Abstract:
The endogenous synthesis of arginine (Arg) is a complex multi-organ process in which ornithine (Orn) is converted into citrulline (Cit) which is the immediate precursor for arginine synthesis. To investigate the origin of the Orn used for Cit (and thus Arg) production in mice, a series of primed-continuous infusions of Cit, Orn, and its precursors (Arg, proline (Pro), and glutamate (Glu)) labeled with stable isotopes were conducted for 4 h in the postabsorptive state. Entry rates (Ra) of the different amino acids in plasma were calculated by isotopic dilution and were (mean+/-SEM) RaArg 337+/-9, RaOrn 157+/-10, RaGlu 3336+/-372, RaPro 308+/-21, and RaCit 115+/-6 µmol·kg–1·h–1. Arg was the main precursor for plasma Orn (74±4, 36+/-1 and 10+/-1 µmol·kg–1·h–1 for Arg, Glu and Pro, respectively). In addition Arg released from protein breakdown and metabolized intracellularly, before entering the plasma compartment, may have contributed up to another extra 102+/-8 µmol·kg–1·h–1. Pro, however, was the main precursor for Orn at the site of Cit synthesis (27+/-2, 14+/-1, 12+/-3, and 74+/-4 µmol·kg–1·h–1 for plasma Orn and for Orn synthesized locally from Arg, Glu, Pro, respectively). The use of this novel stable isotope protocol allowed for the determination of two distinct Orn pools, with different precursors, for Cit and Arg synthesis.